| Project/Area Number |
63570105
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
OMORI Kyoko Kansai Med. Univ., Dpt. of Pharmacol., Lecturer, 医学部 (90152256)
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| Co-Investigator(Kenkyū-buntansha) |
OTANI Hitomi Kansai Med. Univ., Dpt. of Pharmacol., Assistant, 医学部, 助手 (40140272)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Adenylate Cyclase / beta-Adrenergic Response / Rat Liver / Cytosolic Factor / GTP-Binding / Peptide / アデニレ-トシクラ-ゼ / β-アドレナリン性応答 / アデニレートシクラーゼ |
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| Research Abstract |
A cytosolic peptide ・ GTP complex which stimulates iota -isoproterenol- responsive adenylate cyclase activity was identified in the rat liver. The peptide component was purified and characterized with regard to its interaction with GTP in the regulation of adenylate cyclase. The peptide was isolated as a complex form with GTP on a Sephadex G-25 column in 1 mM NaHCO_3, and on the same column in 200 mM ammonium acetate it was purified as a dissociated form with Mr -3,000. The purified peptide alone displayed a markedly decreased stimulatory effect on adenylate cyclase activity, but its reassociated form with GTP clearly enhanced the effect of GTP on the enzyme activity. The isoproterenol competition curve using iota -[^3H]dihydroalprenolol (DHA) as an antagonist ligand shifted to lower affinity by the addition of the peptide reassociated with GTP (16.5-fold shift), while the same concentration of GTP (1 mu M) or the peptide alone had little or no effect (1.5- or 0.9-fold shift, respectively). Furthermore, the peptide enhanced the GTP effect in the response to iota -isoproterenol but not in that to glucagon, prostaglandin E_1 and fluoride. These results suggest that the peptide component of the cytosolic activator potentiates the effect of GTP on the agonist- beta -adrenergic receptor-stimulatory guanine nucleotide-binding regulatory component of adenylate cyclase (G_s) (GDP) ternary complex.
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